There is considerable evidence which indicates that the control by the autonomic nervous system of cardiovascular function is compromised with age. As a result of this diminution in neural control, homeostatic mechanisms involved in the regulation of the cardiovascular system become less efficient, and thus contributes to the aging of the organisms. While there are reports which suggest that changes in the end organ itself contribute to the diminished responsiveness to autonomic nervous influences, it is suggested that alteractions in the neurohumoral transmission process are also major factors. To examine this possibility, our experiments will focus on the cardiac adrenergic neuroeffector junction. The studies will be performed in the Fischer 344 male rat, which has been developed specially for studying the aging process in mammals. Isolated for stimulation will be employed. Since end organ responses do not necessarily reflect changes in the status of neurohumoral transmission (the end organ itself may be altered) our experiments will explore modifications in transmission by not only measuring end organ responses (sinoatrial rate) but also by examining the levels of transmitter in the effluent fluid under conditions which take into account local feedback mechanisms, differences in catecholamine metabolic patterns and uptake mechanisms (neuronal and extraneuronal). This will be performed using pharmacological agents. Release of catecholamines by tyramine and by electrical stimulation will be studied in relation to increasing age. Although the experiments are not designed to examine directly changes that may occur in the end organ itself, evaluating the alterations that occur in neurohumoral transmission should indicate to what extent changes in post-junctional events are contributing to the diminution in responsiveness to changes in neural influences. Since pharmacological agents will be used, it is anticipated that further insight into the means by which the aging process may be altered will emerge.